Disease relevance of SOX4

• Differential expression of SOX4 and SOX11 in medulloblastoma [1].
• Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer [2].
• Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2 gamma, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled [3].
• We now show that human SOX4 is expressed in the normal breast and in breast cancer cells [4].
• The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer [5].

High impact information on SOX4

• Syntenin was found to directly associate with the transcription factor Sox4 [6].
• The establishment of neuronal properties is controlled by Sox4 and Sox11 [7].
• Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle [7].
• TLE-1 and BBC3/PUMA were identified as direct targets of SOX4 [2].
• Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene [2].

Chemical compound and disease context of SOX4

• Treatment of T-47D breast cancer cells with the synthetic progestin ORG 2058 directly increased SOX4 transcription, resulting in a 4-fold increase in SOX4 mRNA levels within 4 h of treatment [4].

Biological context of SOX4

• The results presented here demonstrate that the human T cell-specific transcription factor, SOX4, is able to bind to one of these regions; further, SOX4 transactivates transcription of a reporter gene via three tandem copies of this sequence [8].
• The binding of SOX4 to this site is not via a canonical HMG protein binding sequence, identifying a novel class of binding site for this protein [8].
• The high mobility group transcription factor, SOX4, transactivates the human CD2 enhancer [8].
• With somatic cell hybrids, human SOX4 has been mapped to Chromosome (Chr) 6p distal to the MHC region [9].
• Deletion of the DNA-binding domain or trans-activation domain in Sox4 did not significantly affect pro-apoptotic activity, whereas transient transfection of the high mobility group box or the serine-rich region abrogated the apoptotic activity [10].

Anatomical context of SOX4

• When overexpressed in the bladder cell line HU609, SOX4 strongly impaired cell viability and promoted apoptosis [11].
• The detection of SOX4 expression in the normal and malignant breast and the demonstration that SOX4 expression is under progesterone control suggests that changes in SOX4 gene expression may play a role in commitment to the differentiated phenotype in the normal and malignant mammary gland [4].
• The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples [11].
• Furthermore, the identification of naturally processed T cell and Ab epitopes from SOX-4 provides valuable tools for the development of peptide-based vaccination strategies against lung cancer as well as to monitor SOX-4-specific responses in vaccinated patients [5].
• To examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous, and large cell tumor samples as well as in a panel of established small cell and non-small cell lung carcinoma tumor cell lines [5].

Associations of SOX4 with chemical compounds

• Here we describe that the central domain containing glycine-rich region in Sox4, named CD, is a pivotal pro-apoptotic domain to induce apoptotic cell death [10].
• Clones with PRA:PRB ratios greater than 15 were associated with diminished progestin responses on both SOX4 and FAS mRNA expression [12].
• In these cells SOX4 is a progesterone-regulated gene, the expression of which is increased by progestins, leading to a marked increase in SOX-mediated transcriptional activity [4].

Physical interactions of SOX4

• Ubc9 interacts with SOX4 and represses its transcriptional activity [13].

Co-localisations of SOX4

• Furthermore, confocal microscopy showed that Ubc9 co-localized with SOX4 in the nucleus [13].

Regulatory relationships of SOX4

• Luciferase assays found that Ubc9 specifically repressed SOX4 transcriptional activity in 293T cells [13].
• It shows that Ubc9 interacts with SOX4 and represses its transcriptional activity independent of its SUMO-1-conjugating activity [13].

Other interactions of SOX4

• We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas [1].
• There is no evidence for clustering of other members of the SOX1, -2, and -3 or SOX4 gene families around the SOX4 locus [9].
• Assignment of Sox4 to mouse chromosome 13 bands A3-A5 by fluorescence in situ hybridization; refinement of the human SOX4 location to 6p22.3 and of SOX20 to chromosome 17p12.3 [14].
• The SOX-4 gene is a member of a gene family (SOX and SRY) comprising transcription factors that bind to DNA through their high mobility group (HMG)-type binding domain, and previous reports have implicated Sox proteins in various developmental processes [15].
• Deletion mapping demonstrated that HMG-box domain of SOX4 is required to mediate the interaction with Ubc9 in yeast [13].

Analytical, diagnostic and therapeutic context of SOX4

• We show that the SOX4 is overexpressed in prostate tumor samples compared with benign tissues by microarray analysis, real-time PCR, and immunohistochemistry [2].
• Here, we show that Sox4 protein is similarly upregulated in ACC by immunohistochemistry of 28 primary cancers and 20 normal tissues [16].

References